Lipodystrophy Syndrome

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Lipodystrophy Syndrome

In this article

Lipodystrophy is a medical condition characterised by complete or partial loss of adipose tissue. Complete or partial loss of fat (lipoatrophy) may occur in conjunction with pathological accumulation of fat in other distinct regions of the body. Metabolic abnormalities, including insulin resistance, diabetes mellitus, hypertriglyceridaemia, and hepatic steatosis, are frequently associated with lipodystrophy. The extent of fat loss determines the severity of associated metabolic complications.[1]

Lipodystrophy can be inherited or acquired, but inherited lipodystrophic syndromes are very rare.[2, 3]

The lipodystrophies can be divided into generalised, partial or local, depending on the degree and locality of the observable fat loss.[4]

The metabolic effects usually associated with the lipodystrophy syndrome include:[5][6]

The lipodystrophy syndrome associated with antiretroviral treatment (ART) for the human immunodeficiency virus (HIV) infection has been the subject of intense research in recent years.[7]

The rest of this article deals with HIV-related lipodystrophy.

HIV lipodystrophy may co-exist with other metabolic disorders associated with long-term HIV infection, such as raised serum lactate, reduced bone mineral density, hypogonadism and hypertension. It is important because:

The physical changes are obvious and can have many psychologically damaging effects. The condition identifies patients with HIV infection and is thus stigmatising. It has a significant adverse effect on quality of life.[8]

The associated metabolic changes may threaten long-term survival. The management of risk factors for cardiovascular disease is an increasingly important part of the management of HIV infection.[9]

The adverse effect on adherence may compromise management of the HIV infection.

Aetiology

The aetiology is unknown and explanations uncertain and speculative.

A number of factors have been identified as important in cross-sectional studies and it is likely to be caused by an interaction between the HIV infection, the immune recovery and the antiretroviral medication. Both protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitor (NRTI) analogues are implicated, but patients who have never had either have been reported with the syndrome.

Certain antivirals for HIV are associated with a higher relative risk of lipodystrophy syndrome in HIV patients (LDHIV). The highest prevalence is in those who have had PIs and NRTIs together. The highest relative risk is associated with stavudine (d4T) especially if given with didanosine (ddI). Zidovudine (ZDV) is also strongly associated with lipodystrophy syndrome.

Epidemiology

Prevalence

The prevalence in adults varies from 2-60% but for UK adults a recent paper quotes a prevalence of 17%. With increased awareness there are now fewer new cases of LDHIV. A prevalence of 33% has been quoted for highly active antiretroviral therapy (HAART) treated HIV children.[10]

Risk factors

An increased risk of LDHIV is associated with:

Duration of disease.

Gender. Women are at higher risk of LDHIV than men.

Length of treatment and particularly with PIs as described above.

Race. Lipoatrophy is more common in Caucasians.

Presentation

The disease is progressive, becoming more noticeable with duration of disease and length of treatment. The disfigurement can be distressing and stigmatising.

Early treatment and interventions for metabolic changes (as these may promote the LDHIV).

General advice on diet and exercise. This may include use of supplements, high fibre, and omega 3, etc.

Earlier treatment of the HIV infection, may help prevent LDHIV (before AIDS develops and before the CD4 count falls below 200/mm3).

Treatments

It is important that patients should be adequately assessed. Treatment can be divided into:

Lifestyle modification (smoking, diet, exercise). A diet with high protein, trans-fat and less fibre in patients on PIs was linked with LDHIV.[14] A Mediterranean diet, high in omega 3, fresh fruit and vegetables and fibre, is generally recommended. Exercise is also recommended although consistent changes in plasma lipids will not be seen in the short term.[15]

Other measures to improve metabolic parameters:

Metformin may improve the lipids and studies are being undertaken on the glitazones.

Growth hormone has been tried for the lipodystrophy but is expensive and there is a risk of hyperglycaemia.

Statins and fibrates improve the dyslipidaemia but not the lipodystrophy. Simvastatin is contra-indicated because of PI drug interactions. Pravastatin is the most studied. Patients should be referred to a lipid specialist.

Modifying the ART regimen. Decisions should be taken carefully, as changes may affect long-term survival. Unfortunately, there is little evidence on which to base decisions.[16] It may improve the lipodystrophy detectable using imaging techniques but it is not known how durable these changes are. Generally speaking, switching from thymidine analogues (d4T, ZDV) to abacavir (ABC) or tenofovir DF (TDF) has some effect on lipodystrophy.

Corrective procedures. The adverse effects on quality of life, social withdrawal and psychological distress, particularly of facial lipoatrophy, have led to use of skin fillers and implants by plastic surgeons, dermatologists and ear, nose and throat (ENT) surgeons. Some have tried implanting autologous fat cells. The longer-lasting (poly-L-lactic acid- and silicone-based) are favoured over absorbable fillers.[17] Surgery is not an option for the abdominal lipohypertrophy.

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